Some common outcomes to monitor progression and treatment response in clinical care and clinical trials in Duchenne muscular dystrophy (DMD) include strength-based outcomes, e.g., myometry, as well as motor functional tests, e.g., timed function tests, six-minute walk test, and Northstar Ambulatory Assessment (NSAA). The VBP15-002 (n=48 participants; 11 sites in 6 countries) and VBP15-004 (n=121 participants; 33 sites in 11 countries) clinical trials in DMD provided two independent, well-controlled cohorts, with harmonized outcomes and protocols.
To present test-retest reliability of outcomes in two cohorts using screening and baseline measurements.
All outcomes including velocities from three timed tests: stand from supine (TTSTANDV), climb 4 steps (TTCLIMBV), and run/walk 10m (TTRWV) were measured in both cohorts. Two different techniques were used for myometry in VBP15-002 (CINRG Quantitative Measurement System [CQMS]) and VBP15-004 (MicroFET2 handheld digital muscle dynamometer) cohorts. We calculated intraclass correlation and coefficient of variation.
The median number of days between screening and baseline was 28 (min=10 and max = 69; IQR = 8) and 15 (min=2 and max = 28; IQR = 10) days for VBP15-004 and VBP15-002, respectively. Using complete pooled data, for NSAA, we obtained ICC = 0.89 (95% CI = [0.85-0.92]), for TTRWV: 0.88, for TTCLIMBV: 0.87, for SIXMWDIS: 0.76, and for TTSTANDV: 0.68. Higher ICC were obtained for dynamometer as compared to CQMS for knee extensors but not for elbow flexor; however, the confidence intervals were wide and overlapping. Reliability decreased with younger age for TTSTANDV. Removing outliers improved the reliability. %CV did not always agree with ICC trends.
Two cohorts of boys with DMD yielded good reliability for commonly used clinical outcomes. A nuanced comparison of hand-held myometry measurements vs. CQMS emerged. Age, outliers, and test difficulty were found to influence reliability but not days between repeated measurements.